A patient-designed tissue-engineered model of the infiltrative glioblastoma microenvironment.

Glioblastoma is an aggressive brain cancer characterized by diffuse infiltration. Infiltrated glioma cells persist in the brain post-resection where they interact with glial cells and experience interstitial fluid flow. We use patient-derived glioma stem cells and human glial cells (i.e., astrocytes and microglia) to create a four-component 3D model of this environment informed by resected patient tumors. We examine metrics for invasion, proliferation, and putative stemness in the context of glial cells, fluid forces, and chemotherapies. While the responses are heterogeneous across seven patient-derived lines, interstitial flow significantly increases glioma cell proliferation and stemness while glial cells affect invasion and stemness, potentially related to CCL2 expression and differential activation. In a screen of six drugs, we find in vitro expression of putative stemness marker CD71, but not viability at drug IC50, to predict murine xenograft survival. We posit this patient-informed, infiltrative tumor model as a novel advance toward precision medicine in glioblastoma treatment.

Australian surveys on incidence and control of blowfly strike in sheep between 2003 and 2019 reveal increased use of breeding for resistance, treatment with preventative chemicals and pain relief around mulesing.

Blowfly strike or cutaneous myiasis, caused principally by the Australian sheep blowfly Lucilia cuprina is endemic to Australian sheep producing areas and is a major cause of suffering and economic loss. This article reports incidence and control practices as determined by three cross-sectional surveys of Australian sheep farmers covering the years 2003 (n = 1365), 2011 (n = 575) and 2018 (n = 354) with more questions relating to blowfly strike in the latter two surveys. Breech strike was reported at a higher rate than body strike in all survey years. Reported annual incidence of breech strike ranged from 2.2 to 4.7% of sheep nationally with minor differences between ewes and lambs. The incidence of body strike ranged from 1.0 to 7.1% with higher incidence in younger sheep in all years. The use of fixed time routine preventative chemical treatments increased during the survey period (43%, 46% and 66%, in 2003, 2011 and 2018 respectively) with dicyclanil (54%-58%) and cyromazine (23-36%) the main insecticides used for control since 2011. The use of the Mules operation (mulesing) to remove skin wrinkles from the breech area as a preventative modification did not change between 2011 and 2018 (47% in both), however, the use of pain relief at mulesing of replacement ewe lambs increased substantially between 2011 (59%) and 2018 (87%). The most commonly used methods to assist with flystrike control were timing of crutching (clipping of wool from susceptible areas) and shearing, with few respondents destroying maggots from treated sheep (21-26%) and very low use of fly traps (5-8%). Phenotypic selection of ewes for reduced susceptibility to flystrike based on visual traits was practiced by 61% of respondents in 2011 and 56% in 2018. Selection of rams for reduced susceptibility using estimated breeding values increased from 10% in 2011 to 17% in 2018. Breeding for resistance was the most commonly nominated (21%) most important change made to flystrike management in 2018. The results indicate that concern for sheep welfare has increased with almost universal use of pain relief at mulesing. Increased use of selection for blowfly resistance indicates farmer commitment to planning for a future without mulesing, although the practice remains prevalent. An increase in the reliance on preventative chemical treatments increases the risk of insecticide resistance.

Prevalence of sheep lice and trends in control practices across Australia - Australian sheep parasite control surveys from 2003 to 2019.

The sheep body louse (Bovicola ovis) is a parasite of major economic concern in Australia. This article reports lice incidence and control practices on Australian sheep farms as determined by three cross-sectional surveys of the years 2003, 2011 and 2018. The incidence of live lice detected within a flock was similar across the survey years with a slight decline in 2018 (2003: 20%, 2011: 18.6% and 2018: 13.9%). In an average year, most farmers did not see any direct or indirect evidence of lice infestation (2011: 59.3% and 2018: 69.5%), however, over a five-year period 38.9% (2003), 66.3% (in 2011) and 55.8% (in 2018) reported seeing evidence of lice infestation at least once with significant variation between sheep producing regions in 2011. In an average year, nearly three quarters of respondents treated for lice (2011:73.5% and 2018: 73.3%) with the majority treating immediately following shearing and very few treating sheep with long wool. Even higher percentages treated for lice at least once in the preceding five-year period (2011: 86.2% and 2018: 87.5%). Backliner was the most popular method of chemical application for lice control in sheep off-shears or with short wool (2003: 77%, 2011: 73% and 2018: 74.3%). For long wool treatments, hand jetting declined in popularity from 2003 (64%) to 2011 (54%) and 2018 (8.6%) as backliners became more popular (2003: 36%, 2011: 51% and 2018: 60%). The use of benzoylphenyl urea insect growth regulators (IGR) for off-shears/short wool treatment declined from 2003 (92.8%) to 2011 (51%) and 2018 (2.9%) and were largely replaced by neonicotinoids and spinosad for backliner/spray-on products. The use of organophosphates declined for plunge dipping (2003: 83.8%, 2011: 83% and 2018: 7.7%). Spinosad use for plunge dipping off-shears/short wool increased over the survey years (2003, 0%, 2011: 9% and 2018:46.2%). The use of IGRs declined for backliner application on long wool and were mainly replaced by spinosad in 2011 and 2018. Fewer respondents reported suspected resistance to lice control products in 2018 (8%) compared with 2003 (26%) and 2011 (13%) with most reporting suspected resistance to IGR and synthetic pyrethroids and emerging suspicions of resistance to neonicotinoids in 2018. Resistance to lice control products also reduced in importance as a reason for recurring lice infestations between 2011 (ranked 2nd) and 2018 (ranked 6th). Biosecurity was important to sheep producers with the highest ranked reason for recurring lice infestations being from stray or purchased sheep.

International Federation of Nurse Anesthetists' anesthesia program approval process.

The International Federation of Nurse Anesthetists is improving anaesthesia patient care through a voluntary Anesthesia Program Approval Process (APAP) for schools and programmes. It is the result of a coordinated effort by anaesthesia leaders from many nations to implement a voluntary quality improvement system for education. These leaders firmly believe that meeting international education standards is an important way to improve anaesthesia, pain management and resuscitative care to patients worldwide. By 2013, 14 anaesthesia programmes from France, Iceland, Indonesia, Philippines, Sweden, Switzerland, Netherlands, Tunisia and the USA had successfully completed the process. Additional programmes were scheduled for review in 2014. Faculty from these programmes, who have successfully completed APAP, show how anaesthesia educators throughout the world seek to continually improve education and patient care by pledging to meet common education standards. As national governments, education ministers and heads of education institutions work to decrease shortages of healthcare workers, they would benefit from considering the value offered by quality improvement systems supported by professional organizations. When education programmes are measured against standards developed by experts in a profession, policy makers can be assured that the programmes have met certain standards of quality. They can also be confident that graduates of approved programmes are appropriately trained healthcare workers for their citizens.

Guidelines for treatment of lice in sheep with long wool based on a model of the development of wool damage.

OBJECTIVE: This study used a model of the development of wool damage caused by lice in long wool to examine the conditions under which treatment of the sheep is advisable on an economic basis. METHODS: The model uses the proportion of a flock showing visible signs of rubbing and the number of days until the next shearing to compare the cost of treatment (product plus labour) with production losses because of the reduction in wool value caused by lice. From the model output, guidelines are provided to inform producers of the most cost-effective option for lice control. RESULTS: Under normal conditions, if there are any signs of rubbing ≥140 days before shearing, then treatment was the best option. If signs of wool damage are not observed until there are ≤70 days before shearing, then the most cost-effective option is to not treat at all. Between these two periods, the time period in which not treating is the most cost-effective option decreases as the number of sheep visibly affected by lice increases. At higher wool values (A$70/head vs A$35), the option to treat is brought forward approximately 25 days, whereas at a low wool value (A$17.50/head) the period in which no treatment is the most cost-effective is extended by approximately 25 days. Treating only the visibly affected sheep is the best option only for a very short time for all wool values and treatment costs. CONCLUSION: The model provides guidelines for control of lice in long wool to minimise the net cost of infestation and limit unnecessary pesticide use.

Estimating the incidence of fly myiases in Australian sheep flocks: development of a weather-driven regression model.

The blowfly, Lucilia cuprina Wiedemann (Diptera: Calliphoridae), is the primary myiasis (strike) fly of sheep in Australia. Most strike occurs in the anal-perineum area (crutch), but strike to the neck, shoulders, back and withers (body) is also important. Regression analysis was used to determine the extent to which the weekly incidence of flystrike can be explained by variations in fly abundance and/or recent changes in weather, pasture conditions or flock management. Strike and flock management data were collected by questionnaire surveys of 30-60 sheep properties in each of three major sheep-producing areas in southeastern Australia, namely, Gunning (southern New South Wales), Inverell (northern New South Wales) and Flinders Island (Bass Strait). After using simulation modelling to remove effects due to shearing, crutching and/or insecticide treatment, pasture growth index was found to be the most important explanatory variable affecting the incidence of all forms of myiasis. Others were average weekly air temperature, the amount and frequency of rainfall, relative humidity, dung quality index and a factor denoting seasonal effects. Together, these variables accounted for 48.4% of the variation in body strike, 56.8% of that in crutch strike and 51.9% of that in other forms of strike. Prediction was improved by the inclusion of additional lagged variables describing previous strike, fly abundance and fly activity. With these additions, the variation explained increased to 60.4% for body strike, 68.0% for crutch strike and 58.3% for other strikes.

Blowfly succession from possum (Trichosurus vulpecula) carrion in a sheep-farming zone.

The significance of brushtail possum, Trichosurus vulpecula Kerr (Diprotodontia: Phalangeridae) carcasses to the succession and production of Diptera species and its relevance to fly strike management in Tasmania, Australia was examined. Calliphora stygia (Fabricius), Lucilia sericata (Meigen) and Calliphora vicina Robineau-Desvoidy (Diptera: Calliphoridae) were found to be the most abundant and Lucilia cuprina (Wiedemann) (Diptera: Calliphoridae) always the least abundant (< 1%) of the putative primary fly invading species to emerge. Carcasses that were left for up to 15 days in the field before being exposed to flies for 2 days also acted as breeding sites for large numbers of all primary fly species, with the exception of L. cuprina. Ordination analysis revealed no relationship between possum carcasses according to their length of exposure but did show significant negative associations between the number of putative secondary invaders (Chrysomya rufifacies (Macquart) (Diptera: Calliphoridae), Chrysomya varipes (Macquart) (Diptera: Calliphoridae) and putative tertiary flies (Hydrotaea rostrata Robineau-Desvoidy (Diptera: Muscidae)) to the number of C. vicina or C. stygia to emerge. There was enormous variability in the numbers of secondary/tertiary fly species to emerge from carcasses (0-11 450) that negatively correlated with the proportion of all flies to emerge that were primary, and with the mean size of adult L. sericata. Although carcass temperatures, especially those with a large larval population, were elevated, this did not appear to result in significant pre-adult fly mortality. The most important primary fly strike species L. cuprina was only found in insignificant numbers, whereas three other members of the fly strike fauna C. stygia, L. sericata and Ch. rufifacies did use possum carrion as an important breeding resource, but left implications for fly strike management inconclusive.

The National Commission on Nurse Anesthesia Education 10 years later--Part 2: Years following the commission (1994 to present).

In 1989, the National Commission on Nurse Anesthesia Education was implemented to reverse a severe shortage of CRNAs. The Commission, charged with scrutinizing all aspects of nurse anesthesia educational programs, developed 8 goals with corresponding strategies that were used by the Commission Implementation Task Force to actualize its charge. These goals and strategies contributed to an increase of annual graduates from nurse anesthesia programs and the development of 10 new programs. These activities were documented in Part 1 of this article, which appeared in the October 2001 AANA Journal. Following completion of the 3-year project, the Council on Accreditation of Nurse Anesthesia Educational Programs (COA) and the AANA Education Committee began carrying out the final recommendations made by the Commission. Part 2 addresses the accomplishments of the Education Committee and COA in implementing the recommendations of the Commission, discusses current status of educational programs and CRNA manpower, and identifies roles for both educators and practitioners in protecting the future of the profession.

TheNational Commission on Nurse Anesthesia Education 10 years later--Part 1: The commission years (1989-1994).

The significant decrease in the number of anesthesia providers during the late 1980s prompted American Association of Nurse Anesthetists (AANA) leaders to establish the National Commission on Nurse Anesthesia Education (NCNAE). The NCNAE was charged with scrutinizing all aspects of nurse anesthesia educational programs and developing strategies to reverse the critical shortage of nurse anesthetists. The tactics outlined by the commissioners were implemented, and they resulted in an increase of annual nurse anesthesia program graduates. Although there has been continued realization of NCNAE strategies, 10 years later the critical shortage of CRNAs has resurfaced. This 2-part article describes the commission years, the years that followed, and the current status of Certified Registered Nurse Anesthetist (CRNA) manpower.

Nurse anesthetists' perspectives on improving the anesthesia care of culturally diverse patients.

This paper reports the findings from a study which investigated whether the personal experiences of graduate and student nurse anesthetists could provide information on ways to improve the anesthesia care of culturally diverse patients. The study was designed as an exploratory descriptive qualitative investigation involving interviews with informants who were nurse anesthetists from cultural groups other than the dominant group of Anglo-Americans in a large midwestern city in the United States (US). Information emerged from the data that provided pertinent considerations for the provision of culturally congruent nursing care.

Organophosphorus residues in wool grease resulting from specified on-farm lice and flystrike control treatments.

OBJECTIVE: To investigate wool organophosphorus concentrations resulting from a range of farm pesticide application methods. DESIGN: Random sampling of wool for pesticide residues and on-farm interviews to determine associated treatments. PROCEDURE: Tasmanian fleece wool lots were sampled at random and tested for organophosphorus residues. The grower was identified and the pesticide treatments applied to the sheep were ascertained by on-farm interview. RESULTS: The residue concentrations showed a large variation that was not accounted for by differences in treatments by growers. Organophosphorus concentrations were proportional to the number of treatments applied, and inversely related to the time between pesticide application and the subsequent shearing, and were significantly influenced by the method of application. After allowing for the time of application, plunge dipping resulted in pesticide residue concentrations 2 to 2.5 times greater than shower dipping, using spray races or hand jetting, and the use of these methods caused larger residues than the use of jetting races. CONCLUSIONS: We recommend that plunge or shower dipping should not be used more than 7 weeks after shearing, nor at higher concentration than the standard dose rate used for lice control, whereas jetting may be satisfactory for up to 7 months after shearing, provided only one application is administered.

The future of education and accreditation.

This information was originally presented during the AANA Annual Meeting in August 1996. Accreditors and educators are urged to plan for the future and maintain quality education by anticipating changes in the work and educational environments. Successful adaptation to change will be critical to the future of education and accreditation. A number of factors serving as catalysts to change are described.

Nurse anesthesia and multiculturalism.

Program directors from 90 accredited nurse anesthesia programs in the United States and Puerto Rico were surveyed concerning multicultural issues. This article summarizes the identified needs of clients and student nurse anesthetists from culturally diverse backgrounds. Noteworthy findings include the perception that clients were more disadvantaged than students because of differences in socioeconomic status; the fact that about half of the programs provided students with instruction on cultural differences; and the observation that specific units of instruction within courses were the most frequent way of giving instruction in this subject area.

The computer database for nurse anesthesia education programs.

Closures of nurse anesthesia educational programs and a resulting shortage of nurse anesthetists were the focus of a study by the National Commission on Nurse Anesthesia Education. This study occurred simultaneously with the implementation of an accreditation requirement for the submission of Annual Reports by the Council on Accreditation of Nurse Anesthesia Educational Programs (COA). Both groups recognized a need for routine collection of information about educational programs and the result was a cooperative effort between the AANA Education and Research Department and the COA to establish a computer database for public purposes. This article reviews the need for information, describes the Annual Report, and explains the functions and creation of the database.

Should student nurse anesthetists be required to administer regional anesthesia?

Although millions of anesthetics are administered by Certified Registered Nurse Anesthetists (CRNAs) every year, all CRNAs are not trained in the actual administration of regional anesthesia. Some individuals believe that all students should receive this instruction while enrolled in nurse anesthesia education programs. This belief has resulted in the Council on Accreditation of Nurse Anesthesia Educational Programs being encouraged to adopt an accreditation requirement for the administration of regional anesthesia by students. Clinical experience in administration would supplement experience in managing regional anesthetics and didactic instruction that students do receive. This study identified the current practices in nurse anesthesia programs related to the administration of regional anesthesia by students and reasons for supporting or opposing an accreditation requirement.

Causes of preweaning mortality on a large intensive piggery.

Causes of preweaning mortality were examined on a large intensive piggery. Diagnosis was made using comprehensive clinical histories combined with post-mortem data. Two thousand four hundred and twenty-six piglets were born in 238 litters. Pre-parturient and parturient losses were 2.9% and 5.4% of the total numbers of piglets born. Birth to weaning mortality was 11.3%. Among piglets born alive, overlaying was the most frequent cause of death (2.1%), followed by deaths due to diarrhoea (1.7%), anaemia (1.2%), savaging (1.1%) and losses of small weak piglets (0.9%). Most deaths, including stillbirths, were associated with below average birth weight, and two-thirds of all deaths of liveborn pigs occurred within 4 days of birth. Increased litter size resulted in decreased birth weights, an increased percentage of stillborn piglets and mummified foetuses, but duration of parturition was not affected. Stillborn piglets were born late in the litter and after a longer interval between pigs born (interpig interval). Over 70% of deaths due to overlay were in previously healthy piglets, but some were associated with illness of the sow (18%) or both sow and piglet (3%). Savaging was confined mainly to first parity sows and was responsible for 20% of all deaths in these litters. Sixty-two per cent of all piglets with a birth weight of less than 800g were stillborn or died before weaning compared with 18.7% mortality for all piglets. Anaemia in piglets was considered to be due to umbilical haemorrhage. Anaemic piglets had a 36% mortality to weaning compared with 10% for non-anaemic piglets.(ABSTRACT TRUNCATED AT 250 WORDS)

Biochemistry of natural and amprolium-induced polioencephalomalacia in sheep.

Polioencephalomalacia (PEM) induced in sheep was compared with the disease found in naturally occurring cases. Blood biochemical indicators measured were pyruvate, lactate, glucose, erythrocyte transketolase (TK) and stimulation of TK by addition of thiamine pyrophosphate (TPP effect). Faeces and rumen contents were assayed for thiaminase activity. The effect of treating affected sheep with thiamine was also noted. It was found that amprolium treatment could induce thrombocytopenia, but once the sheep became accustomed to amprolium in the diet they seemed to be resistant to this effect. In sheep receiving amprolium significant weight losses preceded the onset of clinical signs. Further weight loss continued throughout the recovery period despite removal of amprolium from the diet and treatment with thiamine. Blood glucose was variable, and was elevated only when marked clinical signs were present. Pyruvate and lactate levels showed marked variation throughout the trial. TK values were depressed and TPP effects increased well before the onset of clinical signs, although some naturally occurring cases had normal levels. Faecal thiaminase activity was negligible in all the sheep on the amprolium trial but most field cases had a high level. High faecal thiaminase was observed in about 5% of clinically normal animals from affected flocks. Depression of erythrocyte TK activity coupled with the presence of faecal thiaminase appeared to be the most reliable diagnostic biochemical parameters for PEM. Treatment of PEM affected sheep with thiamine rapidly brought the biochemical status of the animals to normal. However where advanced brain lesions were present the damage was permanent and such sheep treated with thiamine remained partially decorticate.

Inherited pyruvate kinase deficiency and normal haematologic values in Australian Basenji dogs.

We have carried out a survey to determine the prevalence of carriers of pyruvate kinase deficiency haemolytic anaemia in Basenjis in Victoria. Of 186 dogs tested, 20 were found to be carriers for pyruvate kinase deficiency, a prevalence similar to that reported overseas. Of the 20 carriers found, 17 were born in Australia and were traced directly to 1 of the 3 imported carriers. Despite the relatively high frequency of carriers, no mating of 2 carriers has yet been detected and no dogs with haemolytic anaemia have been observed. The inheritance of the pyruvate kinase deficiency has been traced through up to 5 generations of dogs in Australia and is consistent with co-dominance for pyruvate kinase activity and with an autosomal recessive gene for haemolytic anemia.